title: Isatis indigotica induces hepatocellular cancer cell death via caspase-independent apoptosis-inducing factor translocation apoptotic pathway in vitro and in vivo.
abstract: Isatis indigotica is a biennial herbaceous cruciferous medical herb with antipyretic, antiviral, anti-inflammatory, and anti-endotoxin activity. This study explored the chemotherapeutic potential of I indigotica on human hepatoma cells and investigated the mechanism by which metabolites from I indigotica inhibit hepatoma cell growth. Antitumor activity was discovered in dried I indigotica leaf chloroform extracts (CEDLI). In nude mice xenotransplanted with human hepatoma cells, CEDLI supplementation inhibited tumor growth by ~40% compared with nonsupplemented animals without affecting body weight/food intake. CEDLI induced sub-G1 cell cycle arrest and apoptosis in hepatoma cells. Furthermore, CEDLI activates p53 and Bax, reduces Bcl-2 expression, and causes mitochondrial stress and the release of apoptosis-inducing factor into the cytosol followed by its translocation into the nucleus, resulting in hepatoma cell apoptosis. This study provides novel in vivo evidence of I indigotica's antitumor activity. The chemotherapeutic activity against human hepatoma tumorigenesis was because of a distinguished caspase-independent apoptotic pathway.
authors.affiliation: National Chung Hsing University, Taichung, Taiwan.
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Chung
authors.forename: Feng-Yao
authors.initials: FY
authors.lastname: Tang
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Chung
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Jong
authors.forename: Shih-Shiung
authors.initials: SS
authors.lastname: Chen
authors.forename: Ching-Hsiu
authors.initials: CH
authors.lastname: Tsai
authors.forename: En-Pei
authors.initials: EP
authors.lastname: Chiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004435:Eating / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D031219:Isatis / Q000737:chemistry*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; C494826:BAX protein, human; D061945:Caspase Inhibitors; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases